The objectives of this research program are: 1) to define the neurological mechanisms operating at the hypothalamic level to control vasopressin (VP) release, 2) to ascertain the relationship of these control mechanisms to the osmotic regulation of VP release, and 3) to evaluate the hypothesis that VP release from the posterior pituitary into the peripheral circulation is regulated differently than VP release from the median eminence into the hypophyseal portal circulation. Two hypothalamic, organ-cultured explant systems will be used in these studies: the hypothalamo-neurohypophyseal system (HNS) and the paraventricular nucleus-median eminence system (PVN). The effect of various agents on VP release from these explants will be monitored with a VP radio-immunoassay. Specific agents to be evaluated are neurotransmitters, centrally active brain peptides, prostaglandins, and agents used clinically in the treatment of abnormalities for VP release. Effects of these agents on basal and osmotically stimulated VP release from the posterior pituitary (HNS explant) will be compared to their effects on VP release from the median eminence (PVN explant).